IgA Nephropathy Linked to Elevated Risk of Depression, Anorexia Nervosa

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A study implementing two-sample Mendelian randomization (TSMR) revealed a positive causal relationship between IgA nephropathy and depressive disorder, as well as a potential positive causal relationship with anorexia nervosa. However, no connections were found with the other neuropsychiatric disorders evaluated, including bipolar disorder, schizophrenia or Alzheimer’s disease.

IgA nephropathy is a leading cause of chronic kidney disease and end-stage renal disease (ESRD). Recent research has shown that even among patients undergoing treatment, about 50% still progress to ESRD within a 30-year span.

Neuropsychiatric disorders are conditions that negatively impact a patient’s mental and psychological functioning. Not only do they cause distress to both mental and physical health, they also create a significant economic strain on families and society as a whole. Patients with chronic kidney disease are often diagnosed with neuropsychiatric disorders, such as depression, anxiety and cognitive impairments.

According to the 2019 Global Disease Burden report, neuropsychiatric disorders are rated among the top ten contributors to the global disease burden. However, some researchers believe the full impact of these disorders may be greatly underestimated due to the strict criteria used to define mental illnesses.

“Despite the fact that many contemporary studies affirm the connection between kidney diseases and neuropsychiatric disorders, and the underlying mechanisms have been reasonably explained to some extent, there is a lack of research focusing on more specific pathological subtypes of kidney diseases and their association with neuropsychiatric disorders,” wrote a team of Chinese investigators.

Investigators sought to determine genetic associations between IgA nephropathy and neuropsychiatric disorders to potentially prevent the development of these conditions using a database search that included 15,587 patients and 462,197 controls. Outcome factors were the five common neuropsychiatric disorders (depressive disorder, anorexia nervosa, schizophrenia, bipolar disorder and Alzheimer’s disease) and data were collected from five datasets.

The analysis showed patients with IgA nephropathy may have a slightly higher risk of developing depression. Although no studies were identified that examined the link between anorexia nervosa and IgA nephropathy, there were studies that showed anorexia can impact the kidneys, including an increased risk of chronic kidney disease and acute kidney injury, kidney stones and electrolyte abnormalities. An additional study showed 60% of adolescents diagnosed with eating disorders and concomitant depression, which led investigators to hypothesize that IgA nephropathy and anorexia may involve depressive disorder as an intermediate factor.

However, these relationships were not found with schizophrenia, bipolar disorder or Alzheimer’s disease.

Findings suggest that patients with IgA nephropathy may benefit from monitoring for depressive symptoms to support early intervention and management.

Investigators noted limitations of the study, including that all subjects involved were of European descent, which may have reduced generalizability to other populations. Additionally, the specific underlying pathophysiological mechanisms necessitate more in-depth basic and clinical medical research. Despite these limitations, the study provided important information about the relationship between IgA nephropathy and neuropsychiatric disorders, which can be used in future research.

“In the absence of large-scale randomized controlled trials (RCTs) exploring the relationship between IgA nephropathy and neuropsychiatric disorders, this study provides relatively high-level evidence-based medical evidence for the early diagnosis, prevention and treatment of secondary neuropsychiatric disorders in patients with IgA nephropathy,” investigators concluded.